Presynaptic Ca²⁺Entry Is Unchanged during Hippocampal Mossy Fiber Long-Term Potentiation

Abstract

The hippocampal mossy fiber (MF)-CA3 synapse exhibits NMDA receptor-independent long-term potentiation (LTP), which is expressed by presynaptic mechanisms leading to persistent enhancement of transmitter release. Recent studies have identified several molecules that may play an important role in MF-LTP. These include Rab3A, RIM1alpha, kainate autoreceptor, and hyperpolarization-activated cation channel (I(h)). However, the precise cellular expression mechanism remains to be determined because some studies noticed essential roles of release machinery molecules, whereas others suggested modulation of the ionotropic processes affecting Ca2+ entry into the presynaptic terminals. Using fluorescence recordings of presynaptic Ca2+ in hippocampal slices, here we demonstrated that MF-LTP is not accompanied by an increase in presynaptic Ca2+ influx during an action potential. Whole-cell recordings from CA3 neurons revealed long-lasting increases in mean frequency, but not mean amplitude, of miniature EPSCs after the high-frequency stimulation of MFs. These data indicate that the presynaptic expression mechanisms responsible for enhanced transmitter release during MF-LTP involve persistent modification of presynaptic molecular targets residing downstream of Ca2+ entry.

Assessing the roles of presynaptic ryanodine receptors and adenosine receptors in caffeine-induced enhancement of hippocampal mossy fiber transmission

“…Furthermore, previous study demonstrated that forskolin, which raise intracellular cyclic AMP levels and reportedly cause mossy fiber synaptic enhancement (Weisskopf et al, 1994), didn't affect F value significantly (Kamiya et al, 2002).These results exclude the possibility that caffeine-induced presynaptic Ca 2+ increase involves inhibiting effects of caffeine on A1 receptors and phosphodiesterase. Instead, Ca 2+ release from presynaptic ryanodine-sensitive stores likely mediates the action of caffeine.…”

Calcium influx through hyperpolarization-activated cation channels ( I h channels) contributes to activity-evoked neuronal secretion

“…21), we cannot exclude other possibilities, such as a direct link between I h channels and some factor(s) downstream from Ca 2ϩ (21)(22)(23)(24). In addition, although the 30-s hyperpolarization is sufficient to induce AP-induced facilitation of cell secretion, it is not clear whether such hyperpolarization occurs in DRG neurons in vivo.…”

“…One report postulates that I h is responsible for cAMP-dependent LTP because the I h antagonist ZD7288 blocks the LTP (22) whereas two other reports argue that the block could be due to side-effects of ZD7288 so I h is not involved in LTP (23,24).…”

Evidence against GABA Release from Glutamatergic Mossy Fiber Terminals in the Developing Hippocampus

“…C57BL/6J mice and Wistar rats were used in the present study, and treated according to the guidelines for the care and use of laboratory animals of Hokkaido University School of Medicine. Transverse hippocampal slices of 400 m thick were prepared from 4-to 20-d-old mice and rats as described previously (Kamiya et al, 2002). In this study, we denoted mice of age P14 -P20 as "juvenile" mice, and those of age P4 -P6 as "neonatal" mice.…”